4Divison of Health Policy and Management, University of Minnesota, Minneapolis

5Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, United States

Abstract

Background Allopurinol is the most commonly used first-line urate-lowering therapy for the management of gout. Although allopurinol is generally safe, it is associated with severe allopurinol-hypersensitivity syndrome (AHS) (i.e., Steven Johnson Syndrome and Toxic Epidermal Necrolysis). AHS is fatal in up to 30% of cases. Patients with the human leukocyte antigen HLA-B*5801 are at higher risk of developing AHS. The prevalence of HLA-B*5801 and risk of AHS varies by race and is highest in Asians. The 2012 ACR gout guideline recommends testing for HLA-B*5801 in Asians prior to the allopurinol initiation, but the guideline did not take into account its cost-effectiveness.

Objectives We evaluate the cost-effectiveness of testing for HLA-B*5801 prior to initiation of allopurinol according to race.

Methods We modified a previously developed Markov decision model to evaluate the cost-effectiveness of testing for HLA-B*5801 prior to the initiation of allopurinol (300mg) – febuxostat (80mg) sequential therapy compared to treating with allopurinol (300mg) –febuxostat (80mg) sequential therapy without testing. Hypothetical patients in the testing strategy received a polymerase chain reaction test for HLA-B*5801 prior to the initiation of therapy. Patients that tested positive for HLA-B*5801 were assumed to be treated with febuxostat. Patients that tested negative for HLA-B*5801 and those in the no testing strategy were assumed to initially receive allopurinol. We took account of the variation in risk of hypersensitivity by race (Caucasians 0.0003; African Americans 0.0015; Asian Americans 0.0034) and prevalence of HLA-B*5801 by race (Caucasians 0.007; African Americans 0.038; Asian Americans 0.074). Patients on allopurinol could experience a minor (e.g., erythema multiforme minor) or major (e.g., Stevens-Johnson Syndrome) AHS event. Cost and quality-adjusted life years (QALYs) were evaluated over the lifetime of a hypothetical gout cohort. Finally, we conducted a sensitivity analysis to evaluate the effect variation in cost of testing, the prevalence of HLA-B*5801, and background AHS risk on the cost-effectiveness of testing.

Results Given a willingness-to-pay threshold of $110,000 per QALY, HLA-B*5801 testing is not cost-effective for Caucasians (incremental cost-effectiveness ratio $268,020), but it is cost-effective for African Americans (incremental cost-effectiveness ratio $91,870) and Asian Americans (incremental cost-effectiveness ratio $64,140). As the prevalence of HLA-B*5801 increases the incremental cost-effectiveness ratio of testing decreases (Figure 1). When the prevalence of HLA-B*5801 is greater than 0.029 testing is cost-effective.

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